Optimizing the Live Attenuated Influenza A Vaccine Backbone for High-Risk Patient Groups.
high-risk patient
influenza
live attenuated vaccine
optimization
vaccine
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
26 10 2022
26 10 2022
Historique:
pubmed:
4
10
2022
medline:
29
10
2022
entrez:
3
10
2022
Statut:
ppublish
Résumé
Together with inactivated influenza vaccines (IIV), live attenuated influenza vaccines (LAIV) are an important tool to prevent influenza A virus (IAV) illnesses in patients. LAIVs present the advantages to have a needle-free administration and to trigger a mucosal immune response. LAIV is approved for healthy 2- to 49-year old individuals. However, due to its replicative nature and higher rate of adverse events at-risk populations are excluded from the benefits of this vaccine. Using targeted mutagenesis, we modified the nonstructural protein 1 of the currently licensed LAIV in order to impair its ability to bind the host cellular protein CPSF30 and thus its ability to inhibit host mRNA poly-adenylation. We characterized our optimized LAIV (optiLAIV) in three different mouse models mimicking healthy and high-risk patients. Using a neonatal mouse model, we show faster clearance of our optimized vaccine compared to the licensed LAIV. Despite lower replication, optiLAIV equally protected mice against homosubtypic and hetesubtypic influenza strain challenges. We confirmed the safer profile of optiLAIV in Stat1
Identifiants
pubmed: 36190240
doi: 10.1128/jvi.00871-22
pmc: PMC9599596
doi:
Substances chimiques
Influenza Vaccines
0
Antibodies, Viral
0
Vaccines, Attenuated
0
Vaccines, Inactivated
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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